A REVIEW New frontiers in biological halogenation

The synthesis of halogenated compounds in biological systems is well established, yet the mechanisms by which these compounds are formed are poorly understood. Many commercially important compounds, such as pharmaceuticals and agrochemicals, contain halogens; indeed some halogenated natural products, such as the antibiotic vancomycin, are themselves valuable. Furthermore, several environmentally significant organohalogens can be formed naturally, for example it is likely that a significant proportion of the atmospheric bromomethane is produced by higher plants (Gan et al. 1998). While chemical synthesis of organohalogens can be difficult, the biological production of these compounds occurs under relatively mild conditions and often with a greater degree of specificity. Therefore an understanding of the biosynthesis of halometabolites, and in particular, the enzymology of carbon–halogen bond formation, may provide convenient biotechnological methods for the halogenation of organic compounds. For over 30 years haloperoxidases were the only halogenating enzymes that had been identified and it was largely accepted that these enzymes were responsible for almost all biological halogenation reactions. However, in recent years evidence has accumulated pointing to the existence of other halogenases and now the nature of these enzymes is being revealed. This review concentrates on the occurrence, mechanism and biocatalytic potential of the halogenating enzymes that are currently known. 2. HALOMETABOLITES